Acquired somatic mutations in the microsatellite DNA, in children with bronchial asthma

• Published in: Pediatric pulmonology Vol. 44; no. 10; pp. 1017 - 1024
• Main Authors: Thomou, Christina, Paraskakis, Emmanouil, Neofytou, Eirini, Kalmanti, Maria, Siafakas, Nikolaos M., Tzortzaki, Eleni G.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.10.2009; Wiley-Liss
• Subjects: Adolescent; Age Factors; Asthma - diagnosis; Asthma - genetics; Biological and medical sciences; Blood Chemical Analysis; Case-Control Studies; Child; childhood asthma; Chronic obstructive pulmonary disease, asthma; DNA - analysis; DNA - genetics; Female; Forced Expiratory Volume; General aspects; Genetic Predisposition to Disease; genetic susceptibility; Histocytochemistry; Humans; induced sputum; loss of heterozygosity; Loss of Heterozygosity - genetics; Male; Medical sciences; Microsatellite Instability; Mutation; Pneumology; Probability; Reference Values; Respiratory Function Tests; Severity of Illness Index; Sex Factors; somatic mutations; Sputum - chemistry; Sputum - cytology; Pediatrics; microsatellite instability; Acquired; Pathogenesis; childhood asthma; Genetic determinism; Microsatellite DNA; Predisposition; induced sputum; Bronchus disease; Genetics; Obstructive pulmonary disease; genetic susceptibility; Child; Pneumology; Human; Lung disease; Respiratory disease; Bronchus; Asthma; somatic mutations; Sputum; Loss of heterozygosity; Instability; Mutation
• ISSN: 8755-6863; 1099-0496; 1099-0496
• DOI: 10.1002/ppul.21097

Objectives High incidence of genetic alterations at the microsatellite (MS) DNA level has been reported in asthmatic adults. Working Hypothesis The aim of this study was to investigate whether microsatellite instability (MSI) and loss of heterozygosity (LOH) were detectable phenomena in children with asthma. Methodology DNA was extracted from sputum and blood cells of 27 children (10.8 ± 2.5 years) with mild to moderate asthma, and from 8 healthy, never‐smoked young adults. Fourteen polymorphic MS markers, namely D5S207, D5S820, D5S637, D6S344, D6S2223, D6S263, SGC35231, D11S1253, D11S1337, D11S97, USAT24G1, D13S273, D14S258, and D14S292, located on chromosomes (chr) 5q, 6p, 11q, 13q, and 14q were used to assess MSI and LOH. Results None of the healthy subjects exhibited any genetic alteration. Five out of 27 children (18.5%) exhibited MSI or LOH in sputum cells versus blood samples from which 3 in the marker USAT24G1 (chr 13q14.1), 1 in the marker D14S258 (chr 14q23‐q24.3), and 1 in the marker D5S637 (chr 5q12‐q13). Compared to a previous study, with asthmatic adults, whereas MSI and/or LOH was exhibited in ∼60% of the cases, the current study reported <20% of genetic alterations, at the MS DNA, in asthmatic children. Conclusions Our results showed that genetic instability in the MS DNA, is present in asthmatic children, but to less extent than in adult asthmatics from previous studies. These findings may support the hypothesis that somatic mutations may be early acquired in the natural course of asthma and could represent another contributor to the molecular pathogenesis of the disease. However, further studies are needed to clarify this hypothesis. Pediatr Pulmonol. ©2009 Wiley‐Liss, Inc.